Upfront whole brain radiotherapy for multiple brain metastases in patients with EGFR-mutant lung adenocarcinoma

Changhui Li,1 Jindong Guo,2 Lei Zhao,2 Fang Hu,1 Wei Nie,1 Huimin Wang,1 Xiaoxuan Zheng,1 Yinchen Shen,1 Ping Gu,1 Yujun Zhang,1 Xueyan Zhang11Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China; 2Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of ChinaPurpose: This study aimed to evaluate the efficacy of upfront whole-brain radiotherapy (WBRT) in EGFR-mutant lung adenocarcinoma patients with multiple brain metastases (BM).Methods: In this study, 195 patients with EGFR mutations who had multiple BM at preliminary diagnosis were included and retrospectively reviewed. Patients were admitted to receive the following treatments in a multi-disciplinary setting: upfront WBRT followed by EGFR-TKI, concurrent EGFR-TKI and WBRT and upfront EGFR-TKI followed by WBRT. A disease-specific graded prognostic assessment (DS-GPA) was performed for all the patients. The treatment response and overall survival (OS) were assessed as well.Results: The median OS of these patients was 27 months. Objective response rate (ORR) was significantly better in upfront WBRT group than other two groups (P=0.004). Moreover, patients who received upfront WBRT (n=67) had longer OS than the concomitant group (36 vs 25 months; P=0.006) and the upfront EGFR-TKI group (36 vs 25 months; P<0.0001). The prognosis of patients with different DS-GPA scores significantly differed (P<0.0001). In concomitant group and upfront EGFR-TKIs group, patients with higher DS-GPA scores of 2–3 had more favorable prognosis compared with those with lower DS-GPA scores of 0–1.5 (27 vs 25 months; P=0.023). Patients who received EGFR-TKIs concurrently with WBRT had longer OS than those received upfront EGFR-TKIs with high DS-GPA scores. (37 vs 17 months; P=0.023).Conclusion: The use of upfront WBRT for EGFR-mutated lung adenocarcinoma patients with multiple BM can improve ORR and OS. More importantly, patients with high DS-GPA scores are recommended to receive WBRT immediately after EGFR-TKIs therapy.Keywords: non-small cell lung cancer, brain metastases, EGFR, tyrosine kinase inhibitors, whole brain radiotherap